Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9740 | 29443;29444;29445 | chr2:178706656;178706655;178706654 | chr2:179571383;179571382;179571381 |
| N2AB | 9423 | 28492;28493;28494 | chr2:178706656;178706655;178706654 | chr2:179571383;179571382;179571381 |
| N2A | 8496 | 25711;25712;25713 | chr2:178706656;178706655;178706654 | chr2:179571383;179571382;179571381 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | rs371745586  |
0.556 | 0.961 | None | 0.521 | 0.253 | 0.267299060538 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| N/K | rs371745586 |
0.556 | 0.961 | None | 0.521 | 0.253 | 0.267299060538 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/K | rs371745586 |
0.556 | 0.961 | None | 0.521 | 0.253 | 0.267299060538 | gnomAD-4.0.0 | 2.05252E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.6983E-06 | 0 | 0 |
| N/S | rs753121692 |
0.325 | 0.835 | None | 0.587 | 0.207 | None | gnomAD-2.1.1 | 3.92E-05 | None | None | None | None | I | None | 8.27E-05 | 2.83E-05 | None | 9.66E-05 | 0 | None | 0 | None | 0 | 5.45E-05 | 0 |
| N/S | rs753121692 |
0.325 | 0.835 | None | 0.587 | 0.207 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| N/S | rs753121692 |
0.325 | 0.835 | None | 0.587 | 0.207 | None | gnomAD-4.0.0 | 6.07259E-05 | None | None | None | None | I | None | 1.3344E-05 | 1.66689E-05 | None | 0 | 0 | None | 0 | 0 | 7.96722E-05 | 0 | 3.20174E-05 |
| N/T | None | None | 0.122 | None | 0.227 | 0.175 | 0.272205846399 | gnomAD-4.0.0 | 6.84175E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99437E-07 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.6446 | likely_pathogenic | 0.4199 | ambiguous | -0.043 | Destabilizing | 0.97 | D | 0.573 | neutral | None | None | None | None | I |
| N/C | 0.79 | likely_pathogenic | 0.5726 | pathogenic | 0.132 | Stabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | I |
| N/D | 0.7152 | likely_pathogenic | 0.4915 | ambiguous | 0.331 | Stabilizing | 0.98 | D | 0.557 | neutral | None | None | None | None | I |
| N/E | 0.8931 | likely_pathogenic | 0.7554 | pathogenic | 0.289 | Stabilizing | 0.985 | D | 0.513 | neutral | None | None | None | None | I |
| N/F | 0.8258 | likely_pathogenic | 0.6822 | pathogenic | -0.632 | Destabilizing | 0.999 | D | 0.625 | neutral | None | None | None | None | I |
| N/G | 0.6197 | likely_pathogenic | 0.4274 | ambiguous | -0.158 | Destabilizing | 0.985 | D | 0.56 | neutral | None | None | None | None | I |
| N/H | 0.2775 | likely_benign | 0.168 | benign | -0.136 | Destabilizing | 0.998 | D | 0.529 | neutral | None | None | None | None | I |
| N/I | 0.5655 | likely_pathogenic | 0.3135 | benign | 0.156 | Stabilizing | 0.989 | D | 0.611 | neutral | None | None | None | None | I |
| N/K | 0.763 | likely_pathogenic | 0.5298 | ambiguous | 0.247 | Stabilizing | 0.961 | D | 0.521 | neutral | None | None | None | None | I |
| N/L | 0.5052 | ambiguous | 0.3325 | benign | 0.156 | Stabilizing | 0.97 | D | 0.565 | neutral | None | None | None | None | I |
| N/M | 0.6926 | likely_pathogenic | 0.5054 | ambiguous | 0.11 | Stabilizing | 1.0 | D | 0.589 | neutral | None | None | None | None | I |
| N/P | 0.7375 | likely_pathogenic | 0.5901 | pathogenic | 0.115 | Stabilizing | 0.999 | D | 0.58 | neutral | None | None | None | None | I |
| N/Q | 0.6974 | likely_pathogenic | 0.5237 | ambiguous | -0.196 | Destabilizing | 0.999 | D | 0.515 | neutral | None | None | None | None | I |
| N/R | 0.7467 | likely_pathogenic | 0.5565 | ambiguous | 0.281 | Stabilizing | 0.996 | D | 0.471 | neutral | None | None | None | None | I |
| N/S | 0.1596 | likely_benign | 0.0973 | benign | -0.031 | Destabilizing | 0.835 | D | 0.587 | neutral | None | None | None | None | I |
| N/T | 0.3284 | likely_benign | 0.1858 | benign | 0.059 | Stabilizing | 0.122 | N | 0.227 | neutral | None | None | None | None | I |
| N/V | 0.572 | likely_pathogenic | 0.3563 | ambiguous | 0.115 | Stabilizing | 0.97 | D | 0.549 | neutral | None | None | None | None | I |
| N/W | 0.9428 | likely_pathogenic | 0.8817 | pathogenic | -0.758 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | I |
| N/Y | 0.4712 | ambiguous | 0.2875 | benign | -0.406 | Destabilizing | 0.998 | D | 0.593 | neutral | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.